Scientific Publications by FDA Staff

Am J Physiol Heart Circ Physiol 2014 Jul 1;307(1):H80-7

An electrocardiographic sign of ischemic preconditioning.

Meijs LP, Galeotti L, Pueyo EP, Romero D, Jennings RB, Ringborn M, Warren SG, Wagner GS, Strauss DG

Ischemic preconditioning is a form of intrinsic cardioprotection where an episode of sublethal ischemia protects against subsequent episodes of ischemia. Identifying a clinical biomarker of preconditioning could have important clinical implications, and prior work has focused on the electrocardiographic ST segment. However, the electrophysiology biomarker of preconditioning is increased action potential duration (APD) shortening with subsequent ischemic episodes, and APD shortening should primarily alter the T wave, not the ST segment. We translated findings from simulations to canine to patient models of preconditioning to test the hypothesis that the combination of increased [delta (Delta)] T wave amplitude with decreased ST segment elevation characterizes preconditioning. In simulations, decreased APD caused increased T wave amplitude with minimal ST segment elevation. In contrast, decreased action potential amplitude increased ST segment elevation significantly. In a canine model of preconditioning (9 mongrel dogs undergoing 4 ischemia-reperfusion episodes), ST segment amplitude increased more than T wave amplitude during the first ischemic episode [DeltaT/DeltaST slope = 0.81, 95% confidence interval (CI) 0.46-1.15]; however, during subsequent ischemic episodes the T wave increased significantly more than the ST segment (DeltaT/DeltaST slope = 2.43, CI 2.07-2.80) (P < 0.001 for interaction of occlusions 2 vs. 1). A similar result was observed in patients (9 patients undergoing 2 consecutive prolonged occlusions during elective percutaneous coronary intervention), with an increase in slope of DeltaT/DeltaST of 0.13 (CI -0.15 to 0.42) in the first occlusion to 1.02 (CI 0.31-1.73) in the second occlusion (P = 0.02). This integrated analysis of the T wave and ST segment goes beyond the standard approach to only analyze ST elevation, and detects cellular electrophysiology changes of preconditioning.